IgG N-glycans are associated with prevalent and incident complications of type 2 diabetes.

AIMS/HYPOTHESIS: Inflammation is important in the development of type 2 diabetes complications. The N-glycosylation of IgG influences its role in inflammation. To date, the association of plasma IgG N-glycosylation with type 2 diabetes complications has not been extensively investigated. We hypothesised that N-glycosylation of IgG may be related to the development of complications of type 2 diabetes. METHODS: In three independent type 2 diabetes cohorts, plasma IgG N-glycosylation was measured using ultra performance liquid chromatography (DiaGene n = 1815, GenodiabMar n = 640) and mass spectrometry (Hoorn Diabetes Care Study n = 1266). We investigated the associations of IgG N-glycosylation (fucosylation, galactosylation, sialylation and bisection) with incident and prevalent nephropathy, retinopathy and macrovascular disease using Cox- and logistic regression, followed by meta-analyses. The models were adjusted for age and sex and additionally for clinical risk factors. RESULTS: IgG galactosylation was negatively associated with prevalent and incident nephropathy and macrovascular disease after adjustment for clinical risk factors. Sialylation was negatively associated with incident diabetic nephropathy after adjustment for clinical risk factors. For incident retinopathy, similar associations were found for galactosylation, adjusted for age and sex. CONCLUSIONS: We showed that IgG N-glycosylation, particularly galactosylation and to a lesser extent sialylation, is associated with a higher prevalence and future development of macro- and microvascular complications of diabetes. These findings indicate the predictive potential of IgG N-glycosylation in diabetes complications and should be analysed further in additional large cohorts to obtain the power to solidify these conclusions.

Estrategia educativa intercultural para la prevención del cáncer de cuello cérvico uterino en el resguardo de Paujil, Amazonia Colombiana / Intercultural educational strategy for the prevention of cervical cancer in Paujil Resguardo Amazonía colombiana

RESUMEN Los pueblos indígenas siguen sufriendo inequidades, a pesar de los avances relacionados con la protección de la diversidad étnica y cultural, siendo las mujeres uno de los grupos de mayor riesgo, sobre todo, en lo referente a la salud sexual y reproductiva, situación contemplada como un compromiso de acción en los objetivos de desarrollo sostenible. En ese contexto, esta investigación acción participativa buscó construir una estrategia educativa intercultural, sostenible y segura culturalmente que, a propósito de la prevención del cáncer de cuello uterino, aportará al empoderamiento y la conservación de la salud de las mujeres habitantes del resguardo de Paujil -Colombia. La iniciativa surgió de mujeres indígenas preocupadas por mejorar la salud de sus congéneres y un grupo de investigadores. La construcción de una estrategia educativa intercultural representa un reto, pues la pedagogía occidental no necesariamente corresponde a las concepciones de enseñanza aprendizaje de las indígenas del resguardo. Hay dificultades lingüísticas, pues cada etnia tiene su propia lengua. Las indígenas lideresas se convirtieron en las facilitadoras del proceso que se centró más en el uso de la oralidad y encuentros entre mujeres, que se conocen entre sí. Las mujeres prefieren estrategias didácticas basadas en compartir experiencias y el uso de cartillas y videos. El trabajo permitió concluir que cualquier estrategia educativa intercultural que se proponga debe ser específica y acorde a las necesidades de las comunidades.

ABSTRACT Despite the advances related to the protection of ethnic and cultural diversity, indigenous people continue to suffer inequities, with women being one of the groups most at risk, especially concerning sexual and reproductive health, a situation considered as a problem, a commitment to action in the sustainable development goals. In this context, this Participatory action research searched to build an intercultural educational strategy, sustainable and culturally safe, which, concerning the prevention of cervical cancer, would contribute to the empowerment and conservation of the health of the women who live in the Paujil reservation-Colombia. The initiative arose from indigenous women concerned about improving the health of their peers, and a group of researchers. The construction of an intercultural educational strategy represents a challenge since western pedagogy does not necessarily correspond to the teaching-learning conceptions of the indigenous people of the reservation. There are linguistic difficulties because each ethnic group has its language. The indigenous leaders became the facilitators of the process that focused more on the use of orality and meetings between women who know each other. Women prefer a didactic strategy based on sharing experiences, and the use of primers, and videos. The work allowed to conclude that any proposed of intercultural educational strategy must be specific and according to the needs of the communities.

The GenoDiabMar Registry: A Collaborative Research Platform of Type 2 Diabetes Patients.

The GenoDiabMar registry is a prospective study that aims to provide data on demographic, biochemical, and clinical changes in type 2 diabetic (T2D) patients attending real medical outpatient consultations. This registry is also used to find new biomarkers related to the micro- and macrovascular complications of T2D, with a particular focus on diabetic nephropathy. With this purpose, longitudinal serum and urine samples, DNA banking, and data on 227 metabolomics profiles, 77 immunoglobulin G glycomics traits, and other emerging biomarkers were recorded in this cohort. In this study, we show a detailed longitudinal description of the clinical and analytical parameters of this registry, with a special focus on the progress of renal function and cardiovascular events. The main objective is to analyze whether there are differential risk factors for renal function deterioration between sexes, as well as to analyze cardiovascular events and mortality in this population. In total, 650 patients with a median age of 69 (14) with different grades of chronic kidney disease­G1−G2 (eGFR > 90−60 mL/min/1.73 m2) 50.3%, G3 (eGFR; 59−30 mL/min/1.73 m2) 31.4%, G4 (eGFR; 29−15 mL/min/1.73 m2) 10.8%, and G5 (eGFR < 15 mL/min/1.73 m2) 7.5%­were followed up for 4.7 (0.65) years. Regardless of albuminuria, women lost 0.93 (0.40−1.46) fewer glomerular filtration units per year than men. A total of 17% of the participants experienced rapid deterioration of renal function, 75.2% of whom were men, with differential risk factors between sexes­severe macroalbuminuria > 300 mg/g for men OR [IQ] 2.40 [1.29:4.44] and concomitant peripheral vascular disease 3.32 [1.10:9.57] for women. Overall mortality of 23% was detected (38% of which was due to cardiovascular etiology). We showed that kidney function declined faster in men, with different risk factors compared to women. Patients with T2D and kidney involvement have very high mortality and an important cardiovascular burden. This cohort is proposed as a great tool for scientific collaboration for studies, whether they are focused on T2D, or whether they are interested in comparing differential markers between diabetic and non-diabetic populations.

Mortalidad por cáncer de cuello uterino en la amazonia de Colombia / Cervical cancer mortality in the Colombian Amazon

Resumen OBJETIVO: Analizar el pico de mortalidad por cáncer de cuello uterino registrado en 2018 en Guainía, Colombia. MATERIALES Y MÉTODOS: Estudio ecológico basado en los datos de todas las instituciones con información de la morbilidad y mortalidad y atenciones relacionadas con el cáncer de cuello uterino en Colombia, entre enero de 2009 y diciembre de 2019. Se incluyeron todos los datos disponibles para Guainía. Se excluyeron las bases sin datos entre 2016 y 2018. Se analizaron la morbilidad y mortalidad, atenciones y procedimientos, y se compararon con el comportamiento en 2018 respecto de los demás años. RESULTADOS: Las personas atendidas, las atenciones y los procedimientos relacionados con cáncer de cuello uterino disminuyeron en 2016 y 2017. La concentración de atenciones por persona más baja del periodo se dio en 2017. En 2019, aumentó la cantidad de personas con diagnóstico de infección por papilomavirus. CONCLUSIONES: La reducción en el tamiz, las atenciones y los procedimientos relacionados con el cáncer de cuello uterino, en un territorio, puede ocasionar aumentos en la mortalidad por este tipo de cáncer. Es fundamental sostener en el tiempo las acciones de prevención, diagnóstico y tratamiento, para evitar esta mortalidad.

Abstract OBJECTIVE: To analyze the cervical cancer mortality peak, in Guainía, in 2018. MATERIALS AND METHODS: Ecological study. Data from all institutions with cervical cancer morbidity, mortality and attention information in Colombia, between January/2009 and December/2019, were analyzed. All available data for Guainía were included. The databases with no data between 2016 and 2018 were excluded. Morbidity, mortality, attention, and procedures were analyzed, comparing the behavior in 2018 to the other years. RESULTS: Cervical cancer-related patients, care and procedures decreased in 2016 and 2017. The lowest concentration of care per person in the period was in 2017. In 2019, the number of people diagnosed with papillomavirus infection increased. CONCLUSIONS: The reduction in screenings, care and procedures related to cervical cancer, in a territory, can lead to increases in mortality from this type of cancer. It is essential to sustain prevention, diagnosis, and treatment actions over time to avoid this mortality.

Consumption of Alcohol, Tobacco and Psychoactive Substances in Adolescents from an Indigenous Territory in the Colombian Amazon. / Consumo de alcohol, tabaco y sustancias psicoactivas de los adolescentes de un territorio indígena en la Amazonía colombiana.

INTRODUCTION: There are very few studies on the consumption of psychoactive substances (PAS) among young people from indigenous territories and evening or blended learning students. In Inírida, a municipality in the Colombian Amazon, there were concerns about a possible consumption issue that had never been characterised before. OBJECTIVE: To characterise the consumption of alcohol, tobacco and PAS in Inírida among teenage evening and blended learning students. METHODS: The Inter-American Uniform Drug Use Data System (SIDUC) survey developed by the Inter-American Drug Abuse Control Commission (CICAD) was adapted to the cultural context and carried out on 95% of 284 evening and blended learning students (262). Descriptive statistics and multiple correspondence analyses were used. RESULTS: Currently, 59% consume alcohol; 28% tobacco; 21% marijuana; 3% cocaine paste; 1% ecstasy (MDMA); 1% cocaine; and 1% inhalants. Also, 61% believe that drugs are available inside and around the vicinity of their school, and that marijuana (62%) and cocaine paste (35%) are easily acquired. Drugs are most commonly offered in neighbourhoods (56%) and at parties (30%). Those offering the highest quantity of drugs are acquaintances (35%) and friends (29%). And 51% stated that they had participated in preventive activities related to consumption. CONCLUSIONS: The population has a higher consumption of the substances studied in comparison with the national reference, that of Orinoquía and Amazonía, with the exception of cocaine and inhalants. The consumption situation was confirmed, so participatory actions are proposed.

Consumo de alcohol, tabaco y sustancias psicoactivas de los adolescentes de un territorio indígena en la Amazonía colombiana,

Introducción: Existen muy pocos estudios sobre el consumo de sustancias psicoactivas (SPA) en jóvenes de territorios indígenas y en estudiantes semipresenciales o nocturnos. En Inírida, municipio de la Amazonía colombiana, preocupaba un posible problema de consumo nunca caracterizado. Objetivo: Caracterizar el consumo de alcohol, tabaco y SPA en adolescentes de Inírida esco larizados en jornada nocturna y semipresencial. Métodos: Encuesta CICAD/SIDUC, ajustada al contexto cultural, al 95% de los 284 estudiantes de la jornada elegida (n = 262). Se utilizó estadística descriptiva y análisis de corresponden cias múltiples. Resultados: Actualmente consume alcohol el 59%; cigarrillo, el 28%; marihuana, el 21%; basuco, el 3%; éxtasis, el 1%; cocaína, el 1%, e inhalables, el 1%. El 61% considera que en el colegio y alrededores hay disponibilidad de drogas y es fácil conseguir marihuana (62%) y basuco (35%). Se ofrecen drogas con mayor frecuencia en el barrio (56%) y las fiestas (30%). Las personas que más les ofrecen drogas son conocidos (35%) y amigos (29%). El 51% manifiesta haber recibido actividades de prevención del consumo. Conclusiones: La población presenta mayor consumo de las sustancias estudiadas que el refe rente nacional y de la Orinoquía y Amazonía, excepto en cocaína e inhalables. Se corrobora la situación de consumo y se proponen acciones participativas.

Introduction: There are very few studies on the consumption of psychoactive substances (PAS) among young people from indigenous territories and evening or blended learning students. In Inírida, a municipality in the Colombian Amazon, there were concerns about a possible consumption issue that had never been characterised before. Objective: To characterise the consumption of alcohol, tobacco and PAS in Inírida among teenage evening and blended learning students. Methods: The Inter-American Uniform Drug Use Data System (SIDUC) survey developed by the Inter-American Drug Abuse Control Commission (CICAD) was adapted to the cul tural context and carried out on 95% of 284 evening and blended learning students (262). Descriptive statistics and multiple correspondence analyses were used. Results: Currently, 59% consume alcohol; 28% tobacco; 21% marijuana; 3% cocaine paste; 1% ecstasy (MDMA); 1% cocaine; and 1% inhalants. Also, 61% believe that drugs are available inside and around the vicinity of their school, and that marijuana (62%) and cocaine paste (35%) are easily acquired. Drugs are most commonly offered in neighbourhoods (56%) and at parties (30%). Those offering the highest quantity of drugs are acquaintances (35%) and friends (29%). And 51% stated that they had participated in preventive activities related to consumption. Conclusions: The population has a higher consumption of the substances studied in com parison with the national reference, that of Orinoquía and Amazonía, with the exception of cocaine and inhalants. The consumption situation was confirmed, so participatory actions are proposed.

COVID-19 in Grade 4-5 Chronic Kidney Disease Patients.

INTRODUCTION: Chronic kidney disease (CKD) increases the risk of mortality during coronavirus disease 2019 (COVID-19) episodes, and some reports have underlined the high incidence and severity of this infection in dialysis patients. Information on COVID-19 in nondialysis CKD patients is not available yet. CASE REPORTS: Here we present 7 patients with grade 4-5 CKD who developed symptomatic COVID-19; they comprise 2.6% of our 267 advanced CKD patients. The estimated GFR was between 12 and 20 mL/min during the month prior to COVID-19. The 3 major symptoms were fever, cough, and dyspnea, and 5 patients showed bilateral pneumonia. Hydroxychloroquine, azithromycin, ceftriaxone, and steroids were the most frequently prescribed drugs. Two patients needed noninvasive mechanical ventilation. All patients showed minimal to moderate kidney function deterioration during admission, with an eGFR decline below 5 mL/min in 6 cases. No patient required acute dialysis. Six patients were discharged alive and remained dialysis free athe t the time of reporting, and one 76-year-old patient died. CONCLUSIONS: COVID-19 affects grade 4-5 CKD patients, but prognosis may be acceptable if prompt supportive measures are applied. These findings should be confirmed in larger cohorts, and further observations will be needed to understand the full spectrum of clinical features and the optimal approach to COVID-19 in patients with advanced CKD.

Medical labour under neoliberalism: an ethnographic study in Colombia.

OBJECTIVES: In order to increase the knowledge about the impacts of neoliberal market forces on physician's labour, this article's objectives are to analyse how and why the labour of physicians is transformed by neoliberalism, and the implications of these transformations for patient care. METHODS: Ethnographic investigation is carried out through semi-structured interviews with 20 general practitioners at public and private facilities in Colombia. The interviews were contrasted with national studies of physician's labour since the 1960s. A "mock" job search was also simulated. The analysis was guided by Marxian frameworks. The study was approved by a Human Research Ethics Committee, and informed consent was obtained from all participants. RESULTS: The overpowering for-profit administration of the Colombian healthcare system imposes productivity mechanisms on physicians as a result of a deregulated labour market characterized by low salaries, reduced and self-funded social security benefits, and job insecurity. Overworked physicians with reduced autonomy become frustrated for not being able to provide the care their patients need according to clinical standards. CONCLUSIONS: Under neoliberal conditions, medical labour becomes exploitable and directly productive through its formal and real subsumption to Capital. The negative consequences of a progressive loss in physician's autonomy unveil the incompatibility between neoliberal health systems and people's health.

Clinical Profiles in Renal Patients with COVID-19.

The COVID-19 pandemic has led to frequent referrals to the emergency department on suspicion of this infection in maintenance hemodialysis (MHD) and kidney transplant (KT) patients. We aimed to describe their clinical features comparing confirmed and suspected non-confirmed COVID-19 cases during the Spanish epidemic peak. Confirmed COVID-19 ((+)COVID-19) corresponds to patient with positive RT-PCR SARS-CoV-2 assay. Non-confirmed COVID-19 ((-)COVID-19) corresponds to patients with negative RT-PCR. COVID-19 was suspected in 61 patients (40/803 KT (4.9%), 21/220 MHD (9.5%)). Prevalence of (+)COVID-19 was 3.2% in KT and 3.6% in MHD patients. Thirty-four (26 KT and 8 MHD) were (+)COVID-19 and 27 (14 KT and 13 MHD) (-)COVID-19. In comparison with (-)COVID-19 patients, (+)COVID-19 showed higher frequency of typical viral symptoms (cough, dyspnea, asthenia and myalgias), pneumonia (88.2% vs. 14.3%) and LDH and CRP while lower phosphate levels, need of hospital admission (100% vs. 63%), use of non-invasive mechanical ventilation (36% vs. 11%) and mortality (38% vs. 0%) (p < 0.001). Time from symptoms onset to admission was longer in patients who finally died than in survivors (8.5 vs. 3.8, p = 0.007). In KT and MHD patients, (+)COVID-19 shows more clinical severity than suspected non-confirmed cases. Prompt RT-PCR is mandatory to confirm COVID-19 diagnosis.

COVID-19 in elderly kidney transplant recipients.

The SARS-Cov-2 infection disease (COVID-19) pandemic has posed at risk the kidney transplant (KT) population, particularly the elderly recipients. From March 12 until April 4, 2020, we diagnosed COVID-19 in 16 of our 324 KT patients aged ≥65 years old (4.9%). Many of them had had contact with healthcare facilities in the month prior to infection. Median time of symptom onset to admission was 7 days. All presented with fever and all but one with pneumonia. Up to 33% showed renal graft dysfunction. At infection diagnosis, mTOR inhibitors or mycophenolate were withdrawn. Tacrolimus was withdrawn in 70%. The main treatment combination was hydroxychloroquine and azithromycin. A subset of patients was treated with anti-retroviral and tocilizumab. Short-term fatality rate was 50% at a median time since admission of 3 days. Those who died were more frequently obese, frail, and had underlying heart disease. Although a higher respiratory rate was observed at admission in nonsurvivors, symptoms at presentation were similar between both groups. Patients who died were more anemic, lymphopenic, and showed higher D-dimer, C-reactive protein, and IL-6 at their first tests. COVID-19 is frequent among the elderly KT population and associates a very early and high mortality rate.

Condiciones en la frontera sur entre Colombia y Venezuela ante la pandemia de COVID-19 / Underlying conditions on the southern border between Colombia and Venezuela to face the COVID-19 pandemic

RESUMEN Objetivos Dimensionar la migración humana en la frontera sur entre Colombia y Venezuela (Departamento de Guainía), y caracterizar las condiciones sociales, de acceso y de atención en salud frente a la pandemia de COVID-19. Métodos Estudio mixto, epidemiológico y etnográfico. Se calcularon: tasa de migrantes venezolanos (según Migración Colombia al 31 de diciembre de 2019), acceso efectivo a atención médica y dotación en puestos de salud (según datos recolectados entre junio de 2017 y julio de 2019, en todos los puestos de salud de Guainía, mediante entrevistas semiestructuradas, observación participante y el uso de Google Earth™ y Wikiloc™). Los tiempos medianos se calcularon y graficaron en Stata™. Se describieron dinámicas culturales y de atención en salud a partir del trabajo de campo y de una permanente revisión documental. Resultados Guainía ocupa el puesto 23 en número total de venezolanos, pero es el cuarto departamento en densidad de venezolanos (14,4%). En ausencia del centro de salud de San José, en el río Guainía los tiempos medianos hasta la institución de referencia real son de 8,7 horas en invierno y 12,3 en verano y los casos complejos requieren remisión aérea. En el río Inírida, sin el centro de Chorro Bocón, los tiempos reales son de 11,9 horas en invierno y 16,1 en verano. Solo el 57% de los puestos de salud tenía insumos para manejar infección respiratoria aguda. Conclusiones Ante la llegada de COVID-19 a territorios sur-fronterizos, es necesario fortalecer inmediatamente servicios médicos y de salud pública para evitar elevadas tasas de letalidad.(AU)

ABSTRACT Objectives To size human migration on the southern border between Colombia and Venezuela (Guainía department), and characterize the social, access and health care conditions relevant to the COVID-19 pandemic. Methods Mixed epidemiological and ethnographic study. Rate of Venezuelan migrants was calculated according to Migration Colombia data until December 31st, 2019, also effective access to medical care, and provision of health posts were calculated, with information from each Guainía health post collected from June 2017 to June 2019, through semi-structured interviews, participant observations, Google Earth™ and Wikiloc™. Stata™ was used to calculate and graph median times of effective access. Cultural dynamics and health care conditions were described by the field work information and a permanent documentary review. Results Guainía is the 23rd department, according to the total number of Venezuelans, but the fourth in Venezuelans density (14,4%). In the Guainía river, the median times to the real reference health institution were 8,7 hours in winter and 12,3 in summer, and complex cases require air referrals. In the Inírida river, the median times to the real reference health institution were 11,9 hours in winter and 16,1 in summer. Only 57% of the health posts had supplies for acute respiratory infections. Conclusions Facing COVID-19 in south border territories, it is necessary to immediately strengthen medical and public health services to avoid high fatality rates.(AU)

Condiciones en la frontera sur entre Colombia y Venezuela ante la pandemia de COVID-19 / Underlying conditions on the southern border between Colombia and Venezuela to face the COVID-19 pandemic

RESUMEN Objetivos Dimensionar la migración humana en la frontera sur entre Colombia y Venezuela (Departamento de Guainía), y caracterizar las condiciones sociales, de acceso y de atención en salud frente a la pandemia de COVID-19. Métodos Estudio mixto, epidemiológico y etnográfico. Se calcularon: tasa de migrantes venezolanos (según Migración Colombia al 31 de diciembre de 2019), acceso efectivo a atención médica y dotación en puestos de salud (según datos recolectados entre junio de 2017 y julio de 2019, en todos los puestos de salud de Guainía, mediante entrevistas semiestructuradas, observación participante y el uso de Google Earth™ y Wikiloc™). Los tiempos medianos se calcularon y graficaron en Stata™. Se describieron dinámicas culturales y de atención en salud a partir del trabajo de campo y de una permanente revisión documental. Resultados Guainía ocupa el puesto 23 en número total de venezolanos, pero es el cuarto departamento en densidad de venezolanos (14,4%). En ausencia del centro de salud de San José, en el río Guainía los tiempos medianos hasta la institución de referencia real son de 8,7 horas en invierno y 12,3 en verano y los casos complejos requieren remisión aérea. En el río Inírida, sin el centro de Chorro Bocón, los tiempos reales son de 11,9 horas en invierno y 16,1 en verano. Solo el 57% de los puestos de salud tenía insumos para manejar infección respiratoria aguda. Conclusiones Ante la llegada de COVID-19 a territorios sur-fronterizos, es necesario fortalecer inmediatamente servicios médicos y de salud pública para evitar elevadas tasas de letalidad.(AU)

ABSTRACT Objectives To size human migration on the southern border between Colombia and Venezuela (Guainía department), and characterize the social, access and health care conditions relevant to the COVID-19 pandemic. Methods Mixed epidemiological and ethnographic study. Rate of Venezuelan migrants was calculated according to Migration Colombia data until December 31st, 2019, also effective access to medical care, and provision of health posts were calculated, with information from each Guainía health post collected from June 2017 to June 2019, through semi-structured interviews, participant observations, Google Earth™ and Wikiloc™. Stata™ was used to calculate and graph median times of effective access. Cultural dynamics and health care conditions were described by the field work information and a permanent documentary review. Results Guainía is the 23rd department, according to the total number of Venezuelans, but the fourth in Venezuelans density (14,4%). In the Guainía river, the median times to the real reference health institution were 8,7 hours in winter and 12,3 in summer, and complex cases require air referrals. In the Inírida river, the median times to the real reference health institution were 11,9 hours in winter and 16,1 in summer. Only 57% of the health posts had supplies for acute respiratory infections. Conclusions Facing COVID-19 in south border territories, it is necessary to immediately strengthen medical and public health services to avoid high fatality rates.(AU)

[Underlying conditions on the southern border between Colombia and Venezuela to face the COVID-19 pandemic]. / Condiciones en la frontera sur entre Colombia y Venezuela ante la pandemia de COVID-19.

OBJECTIVES: To size human migration on the southern border between Colombia and Venezuela (Guainía department), and characterize the social, access and health care conditions relevant to the COVID-19 pandemic. METHODS: Mixed epidemiological and ethnographic study. Rate of Venezuelan migrants was calculated according to Migration Colombia data until December 31st, 2019, also effective access to medical care, and provision of health posts were calculated, with information from each Guainía health post collected from June 2017 to June 2019, through semi-structured interviews, participant observations, Google Earth™ and Wikiloc™. Stata™ was used to calculate and graph median times of effective access. Cultural dynamics and health care conditions were described by the field work information and a permanent documentary review. RESULTS: Guainía is the 23rd department, according to the total number of Venezuelans, but the fourth in Venezuelans density (14,4%). In the Guainía river, the median times to the real reference health institution were 8,7 hours in winter and 12,3 in summer, and complex cases require air referrals. In the Inírida river, the median times to the real reference health institution were 11,9 hours in winter and 16,1 in summer. Only 57% of the health posts had supplies for acute respiratory infections. CONCLUSIONS: Facing COVID-19 in south border territories, it is necessary to immediately strengthen medical and public health services to avoid high fatality rates.

Mielinolisis extrapontina en una paciente embarazada, con hiperémesis e hiponatremia. Reporte de un caso / Extrapontine myelinolysis in a pregnant with hyperemesis and hyponatremia. A case report

Resumen: ANTECEDENTES: La mielinolisis extrapontina forma parte del síndrome de desmielinización osmótica que lesiona los oligodendrocitos y ocasiona la pérdida de mielina en regiones del sistema nervioso central diferentes al puente del tronco encefálico. Se origina por la corrección rápida de sodio en pacientes con hiponatremia y en mujeres embarazadas se asocia con hiperémesis gravídica. CASO CLÍNICO: Paciente indígena, de 32 años, enviada a un hospital universitario de alta complejidad en Bogotá, desde un territorio de la Amazonia colombiana, en el marco de un nuevo modelo de salud, con embarazo de 15 semanas, quien tuvo un episodio convulsivo, afasia y automatismo bucal, con antecedente de hiperémesis gravídica y otro episodio de hiperémesis con hiponatremia un mes antes. Inicialmente se sospechó eclampsia y neuroinfección; se implementó tratamiento para la corrección rápida del sodio y prescripción de anticonvulsivos. La resonancia magnética cerebral fue compatible con mielinolisis extrapontina. Luego de un mes regresó a su territorio de origen para rehabilitación. Tuvo parto domiciliario a las 38.3 semanas y acudió al hospital para el alumbramiento. CONCLUSIONES: La mielinolisis extrapontina debe considerarse en el diagnóstico diferencial entre embarazo con cuadro neurológico agudo y antecedente de hiperémesis e hiponatremia. Es importante integrar, sistemáticamente, hospitales universitarios o de alta complejidad en los territorios rurales para optimizar el diagnóstico y tratamiento de estas pacientes.

Abstract: BACKGROUND: Extrapontine myelinolysis is part of the osmotic demyelination syndrome, being an acute non-inflammatory demyelinating disease caused by hyperosmotic stress that injures oligodendrocytes and causes myelin loss in regions of the central nervous system other than the pons of the brain stem. Primarily caused by a rapid sodium correction in patients with hyponatremia, in pregnant women its most frequent association is with hyperemesis gravidarum. CLINICAL CASE: A 32-year-old indigenous woman was referred to a university hospital of high complexity, in Bogotá, from a territory of the Colombian Amazon, within the framework of a new health care model, with a 15-week pregnancy, who had a convulsive episode, aphasia and oral automatism, and a recent history of hyperemesis gravidarum. Another history of hyperemesis and hyponatremia a month ago. Initially, eclampsia and neuroinfection were suspected, a rapid correction of sodium, anticonvulsant, remission and management in the intensive care unit was performed. MRI was compatible with extrapontin myelinolysis. After a month she returned to the territory of origin for rehabilitation. She had a home delivery at 38.3 weeks and went to the hospital for placental delivery. CONCLUSION: Extrapontin myelinolysis should be considered in the differential diagnosis between pregnancy with acute neurological symptoms conditions and a history of hyperemesis or hyponatremia. In case of a repeated history of acute hyponatremia in pregnant women with hyperemesis, chronicity should be considered. It is recommended to integrate university hospitals to rural territories to optimize the diagnosis and management of this type of cases.

CADM1, MAL, and miR124 Promoter Methylation as Biomarkers of Transforming Cervical Intrapithelial Lesions.

BACKGROUND: Squamous intraepithelial lesions/cervical intraepithelial neoplasias (SIL/CIN) are high-risk human papilloma virus (hrHPV)-related lesions which are considered as high grade (HSIL/CIN2-3) or low grade (LSIL/CIN1) lesions according to their risk of progression to cervical cancer (CC). Most HSIL/CIN2-3 are considered as transforming hrHPV infections, so truly CC precursors, although some clear spontaneously. hrHPV testing has a high sensitivity for the detection of HSIL/CIN2-3 but a relatively low specificity for identifying transforming lesions. We aimed to determine whether the combination of CADM1, MAL and miR124 promoter methylation status assessed in histological samples can be used as a biomarker in the identification of transforming HSIL/CIN lesions. DESIGN: 131 cervical biopsies, including 8 cases with no lesion and a negative hrHPV test result (control group), 19 low-grade (L)SIL/CIN1, 30 HSIL/CIN2, 60 HSIL/CIN3, and 14 CC were prospectively collected. hrHPV was detected and genotyped using the polymerase chain reaction (PCR)-based technique SPF10 HPV LIPA. A multiplex quantitative methylation-specific PCR (qMSP) was used to identify the methylation status of the CADM1, MAL, and miR124 promoter genes. RESULTS: Significantly higher methylation levels of CADM1, MAL and miR-124 were found in HSIL/CIN2-3 and CC compared with normal and LSIL lesions. DNA methylation of at least one gene was detected in 12.5% (1/8) of normal samples, 31.5% (6/19) of LSIL/CIN1, 83.3% (25/30) of HSIL/CIN2, 81.6% (49/60) of HSIL/CIN3 and 100% (14/14) of CC (p < 0.001). The sensitivity and specificity for HSIL/CIN2-3 and CC of having at least one methylated gene were 84.6% and 74.0%, respectively. The sensitivity and specificity of the combination of at least one methylated gene and a positive hrHPV test were 80.7% and 85.1% for HSIL/CIN2-3 and CC, respectively. CONCLUSIONS: The methylation rate of CADM1, MAL and miR124 increases with the severity of the lesion. Further research is warranted to evaluate the usefulness of these biomarkers for the identification of transforming HSIL/CIN.

Clinicopathological evaluation of the programmed cell death 1 (PD1)/programmed cell death-ligand 1 (PD-L1) axis in post-transplant lymphoproliferative disorders: association with Epstein-Barr virus, PD-L1 copy number alterations, and outcome.

AIMS: The clinical implications of the programmed cell death 1 (PD1)/programmed cell death-ligand 1 (PD-L1) axis in patients with post-transplant lymphoproliferative disorders are largely unknown, and its association with Epstein-Barr virus (EBV) status and PD-L1 copy number alterations (CNAs) has not been thoroughly studied. METHODS AND RESULTS: PD1/PD-L1 expression was studied in 50 adult post-transplant lymphoproliferative disorders, and the correlations with PD-L1 CNAs, EBV, clinicopathological features and outcome were evaluated. Thirty-seven (74%) cases were classified as diffuse large B-cell lymphoma (DLBCL), nine (18%) cases were classified as polymorphic, and four (8%) cases were classified as classic Hodgkin lymphoma. Thirty-four cases were EBV-positive, with 29 of 34 (85%) having latency II or III, and 15 of 34 (44%) having viral replication. PD-L1 expression in tumour cells and tumour-associated macrophages was observed in 30 (60%) and 37 (74%) cases, respectively. PD1 positivity was seen in 16 (32%) cases. PD-L1 expression was associated with EBV with latency II or III (P = 0.001) and organ rejection (P = 0.04), and, in DLBCL, with non-germinal centre type DLBCL (P < 0.001). Cases with PD-L1-positive tumour cells showed a higher number of PD-L1 CNAs than PD-L1-negative cases (P = 0.001). Patients with EBV/latency III/replication and simultaneous PD-L1 expression showed the worst overall survival (P < 0.001). CONCLUSIONS: The PD1/PD-L1 axis is deregulated in post-transplant lymphoproliferative disorders, with frequent PD-L1 expression and PD1 negativity. PD-L1 expression is associated with EBV latency II or III and PD-L1 CNAs, and probably reflects a proinflammatory tumour microenvironment. The combined analysis of EBV status and PD-L1 expression may help to identify deeply immunosuppressed patients who can benefit from immune reconstitution approaches.

Pacientes procedentes de un territorio disperso que fallecieron en un hospital universitario: serie de casos / Patients from a scattered territory who died in a university hospital. A case series / Pacientes de um territorio disperso, que morreram em um hospital universitário. Série de casos

Introducción: Guainía, departamento con población dispersa, pluriétnico y multifronterizo, fue seleccionado en 2016 como piloto del Modelo Integral de Atención en Salud (MIAS). Dentro de la operación del MIAS se encuentra el Hospital de San José (HSJ), hospital universitario ubicado en Bogotá, que recibe pacientes remitidos por aire desde Guainía para atención especializada. Objetivo: Describir las características de los pacientes remitidos de Guainía que murieron en el HSJ, en el marco del MIAS. Métodos: Estudio tipo serie de casos de los pacientes procedentes de Guainía y remitidos al HSJ que fallecieron durante la estancia hospitalaria entre el 1 de julio de 2016 y el 31 de diciembre de 2017. Se analizaron variables demográficas y clínicas mediante estadística descriptiva. Para identificar muertes evitables se usó el inventario de indicadores de mortalidad evitable adaptado a Colombia (INIME). Resultados: De los 238 pacientes recibidos, 18 fallecieron, 3 de los cuales murieron antes de 48 horas de estancia hospitalaria. La mayoría requirió unidad de cuidado intensivo. Entre los diagnósticos de ingreso predominó la neumonía en el grupo de las patologías infecciosas y la desnutrición en las no infecciosas. Las muertes de todos los menores de 18 años y del 70 % de adultos tenían causas potencialmente evitables según los grupos del INIME. Discusión: El predominio de causas de mortalidad evitables, con muertes por desnutrición infantil y enfermedad diarreica aguda, indica la necesidad de actividades que impacten los determinantes sociales y la determinación social de la salud. Conclusión: La alta frecuencia de muertes evitables sugiere que la implementación de la estrategia de atención primaria en salud no fue óptima en el periodo estudiado. Además, para los casos graves, el estrés del desplazamiento aéreo a Bogotá no parece una buena opción. Es necesario incrementar las capacidades del Hospital de Inírida para reducir remisiones de casos.

Introduction: Guainía, a department with a dispersed, multi-ethnic and multi-border population, was selected in 2016 as a pilot of the Integral Model of Health Care (MIAS). Within the MIAS operation is the Hospital de San José (HSJ), a university hospital located in Bogotá, which receives air-remited patients from Guainía for specialized care. Objective: To describe the characteristics of Guainía patients who died in HSJ, under the MIAS. Methods: Serial case study of patients from Guainía referred to HSJ, who died during the hospital stay, between July 01, 2016 and December 31, 2017. Demographic and clinical variables were analyzed using descriptive statistics. The inventory of Colombia-adapted avoidable mortality indicators (INIME) was used to identify preventable deaths. Results: Of the 238 patients received, 18 died, 3 of them died before 48 hours of hospital stay. Most required Intensive Care Unit. Among the entrance diagnoses, pneumonia prevailed in the group of infectious pathologies and malnutrition in non-infectious ones. The deaths of all children under the age of 18 and 70 % of adults had potentially avoidable causes according to INIME groups. Discussion: The prevalence of preventable causes of mortality, with deaths from child malnutrition and acute diarrhoeal disease, indicates the need for activities that impact social determinants and social determination of health. Conclusion: The high frequency of avoidable deaths suggests that the implementation of the Primary Health Care strategy was not optimal in the period studied. Moreover, for severe cases, the stress of air travel to Bogotá does not seem like a good option. It is necessary to increase the capacities of Inírida Hospital to reduce critical case referrals.

Introdução: Guainía, departamento com população dispersa, multiétnica e multi-fronteira, foi selecionado em 2016 como piloto do Modelo de Atenção Integral à Saúde (MIAS). Dentro da operação do MIAS, encontra-se o Hospital San José (HSJ), um hospital universitário localizado em Bogotá, que recebe pacientes encaminhados por via aérea de Guainía para atendimento especializado. Objetivo: Descrever as características dos pacientes encaminhados por Guainía que morreram no HSJ, no âmbito do MIAS. Métodos: Estudo de série de casos de pacientes de Guainia e encaminhados ao HSJ que faleceram durante a internação hospitalar, entre 1 de julho de 2016 e 31 de dezembro de 2017. As variáveis demográficas e clínicas foram analisadas por estatística descritiva. Para identificar mortes evitáveis, foi utilizado o inventário de indicadores de mortalidade evitável adaptados à Colômbia (INIME). Resultados: Dos 238 pacientes recebidos, 18 morreram, 3 dos quais morreram dentro de 48 horas após a internação hospitalar. A maioria necessitava de unidade de terapia intensiva. Entre os diagnósticos de admissão, a pneumonia predominou no grupo de doenças infecciosas e a desnutrição em doenças não infecciosas. As mortes de todos os menores de 18 e 70 % dos adultos tiveram causas potencialmente evitáveis, de acordo com os grupos do INIME. Discussão: A prevalência de causas evitáveis de mortalidade, com mortes por desnutrição infantil e doença diarréica aguda, indica a necessidade de atividades que impactem os determinantes sociais e a determinação da saúde social. Conclusão: A alta frequência de mortes evitáveis sugere que a implementação da estratégia de Atenção Primária à Saúde não foi ótima no período estudado. Além disso, em casos graves, o estresse nas viagens aéreas para Bogotá não parece ser uma boa opção.

Usefulness of the KDPI in Spain: A comparison with donor age and definition of standard/expanded criteria donor / Utilidad del índice KDPI en España: una comparación con la edad del donante y la definición de donante con criterios de selección estándar/ampliados

INTRODUCTION: Kidney donor shortage requires expanding donor selection criteria, as well as use of objective tools to minimize the percentage of discarded organs. Some donor pre-transplant variables such as age, standard/expanded criteria donor (SCD/ECD) definition and calculation of the Kidney Donor Profile Index (KDPI), have demonstrated correlations with patient and graft outcomes. We aimed to establish the accuracy of the three models to determine the prognostic value of kidney transplantation (KT) major outcomes. MATERIAL AND METHODS: We performed a retrospective study in deceased donor KTs at our institution. Unadjusted Cox and Kaplan-Meier survival, and multivariate Cox analyses were fitted to analyze the impact of donor age, SCD/ECD and KDPI on outcomes. RESULTS: 389 KTs were included. Mean donor age was 53.6 ± 15.2 years; 163 (41.9%) came from ECD; mean KDPI was 69.4 ± 23.4%. Median follow-up was 51.9 months. The unadjusted Cox and Kaplan-Meier showed that the three prognostic variables of interest were related to increased risk of patient death, graft failure and death-censored graft failure. However, in the multivariate analysis only KDPI was related to a higher risk of graft failure (HR 1.03 [95% CI 1.01-1.05]; p = 0.014). CONCLUSIONS: SCD/ECD classification did not provide significant prognostic information about patient and graft outcomes. KDPI was linearly related to a higher risk of graft failure, providing a better assessment. More studies are needed before using KDPI as a tool to discard or accept kidneys for transplantation

INTRODUCCIÓN: La escasez de donantes de riñón requiere una ampliación de los criterios de selección de donantes, así como el uso de herramientas objetivas para minimizar el porcentaje de órganos descartados. Algunas variables pretrasplante del donante, como la edad, la definición de donante con criterios de selección estándar/ampliados (standard/expanded criteria donor [SCD/ECD]) y el cálculo del índice del perfil de donante renal (Kidney Donor Profile Index [KDPI]) han demostrado correlación con los resultados del paciente y el injerto. Nuestro objetivo fue evaluar la precisión de 3 modelos diferentes para determinar el valor pronostico en los resultados del trasplante renal. MATERIALES Y MÉTODOS: Llevamos a cabo un estudio retrospectivo de TR de donantes fallecidos en nuestro centro. Se realizó un analisis de supervivencia mediante curvas de Kaplan-Meir y Cox no ajustado, ai como un analisis multivariante de Cox para analizar el impacto de la edad del donante, la definición SCD/ECD y el índice KDPI sobre los resultados. RESULTADOS: Se incluyeron 389 TR. La media de edad de los donantes era de 53,6 ± 15,2 años; 163 (41,9%) procedían de donantes ECD; el índice KDPI medio era de 69,4 ± 23,4%. La mediana de seguimiento era de 51,9 meses. Los análisis de Kaplan-Meier y de Cox no ajustado mostraron que las 3 variables pronósticas de interés estaban relacionadas con un mayor riesgo de muerte del paciente, fracaso del injerto y fracaso del injerto censurado por la muerte. Sin embargo, en el análisis multivariable solamente el índice KDPI estuvo relacionado con un mayor riesgo de fracaso del injerto (HR: 1,03 [IC 95%: 1,01-1,05]; p = 0,014). CONCLUSIONES: La clasificación SCD/ECD no proporcionó información pronóstica significativa sobre los desenlaces del paciente y el injerto. El índice KDPI estuvo linealmente relacionado con un mayor riesgo de fracaso del injerto, por lo que ofrecía una mejor evaluación. Es necesario realizar más estudios antes de usar el índice KDPI como herramienta para descartar o aceptar riñones para trasplante

Value of HPV 16/18 Genotyping and p16/Ki-67 Dual Staining to Predict Progression to HSIL/CIN2+ in Negative Cytologies From a Colposcopy Referral Population.

OBJECTIVES: To assess the prognostic value of human papillomavirus (HPV) 16/18 genotyping and p16/Ki-67 dual staining cytology in high-risk HPV (hrHPV)-positive women with no lesion or minor abnormalities. METHODS: We evaluated progression to high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grades 2 to 3 or cervical cancer (HSIL/CIN2+), persistence/regression of hrHPV infection in women referred to colposcopy showing hrHPV infection, histology diagnosis different from HSIL/CIN2+, and negative cytology. HPV 16/18 genotyping and dual staining were performed in liquid-based cytologic specimens obtained on the first visit. RESULTS: Progression was observed in 16 (8.0%) of 200 women. Those with HPV 16/18 infection had an increased risk of progression compared with women infected by other hrHPV types, and they also showed more persistence. However, no association was observed between progression or persistence and the result of the dual staining. CONCLUSIONS: HPV 16/18-positive women with no lesions or minor abnormalities are at high risk of progression to HSIL/CIN2+ and hrHPV persistence.

Usefulness of the KDPI in Spain: A comparison with donor age and definition of standard/expanded criteria donor.

INTRODUCTION: Kidney donor shortage requires expanding donor selection criteria, as well as use of objective tools to minimize the percentage of discarded organs. Some donor pre-transplant variables such as age, standard/expanded criteria donor (SCD/ECD) definition and calculation of the Kidney Donor Profile Index (KDPI), have demonstrated correlations with patient and graft outcomes. We aimed to establish the accuracy of the three models to determine the prognostic value of kidney transplantation (KT) major outcomes. MATERIAL AND METHODS: We performed a retrospective study in deceased donor KTs at our institution. Unadjusted Cox and Kaplan-Meier survival, and multivariate Cox analyses were fitted to analyze the impact of donor age, SCD/ECD and KDPI on outcomes. RESULTS: 389 KTs were included. Mean donor age was 53.6±15.2 years; 163 (41.9%) came from ECD; mean KDPI was 69.4±23.4%. Median follow-up was 51.9 months. The unadjusted Cox and Kaplan-Meier showed that the three prognostic variables of interest were related to increased risk of patient death, graft failure and death-censored graft failure. However, in the multivariate analysis only KDPI was related to a higher risk of graft failure (HR 1.03 [95% CI 1.01-1.05]; p=0.014). CONCLUSIONS: SCD/ECD classification did not provide significant prognostic information about patient and graft outcomes. KDPI was linearly related to a higher risk of graft failure, providing a better assessment. More studies are needed before using KDPI as a tool to discard or accept kidneys for transplantation.